Glomus Jugulare

Etiology

Glomus jugulare tumors arise from the paraganglia cells located in the adventitia wall of the jugular bulb, within the jugular foramen. They have slow growth and are usually benign. However, due to their location, they can cause a mass effect with invasion and erosion of the temporal bone as they increase in size. Only 1% to 5% are malignant.[2] Eighty percent of paragangliomas are sporadic, with the rest exhibiting a hereditary component.[4] Inherited forms will present with an earlier onset of symptoms and can be bilateral; however, familial forms have a decreased pattern of malignancy when compared to sporadic counterparts.[4]

Epidemiology

The estimated annual incidence of glomus jugulare tumors has been reported to be about 0.07 per 100,000 per year or 1 case per 1.3 million people.[2] The median age at diagnosis is 56 years (44 to 69 years).[5] Female presentation is 3 to 6 times more common than men.[6]

Among head and neck paragangliomas, 44% to 48% are carotid body tumors, 16% to 24% are glomus jugulare, 20% are glomus tympanicum, and 8% are glomus vagale.[7][8]

Pathophysiology

Early-stage paragangliomas present with signs and symptoms related to their location. Specifically, most of these will be related to the involvement of the middle-ear cleft. These neoplasms tend to spread through the hypotympanic air cell tract, around the jugular bulb, inferior petrosal sinus and carotid artery into the jugular foramen and posterior fossa.[4] They can also erode the floor of the hypotympanum, and can, therefore, present as a middle ear mass. If an erosion of the tympanic membrane has occurred, they can also present as an aural polyp or with otorrhagia. Further extension of the tumor through the facial recess, can result in facial nerve encasement and paralysis.[4]

Up to 1 to 3% of glomus tumor cases have secretion of catecholamines.[1] With high enough levels, pheochromocytoma-like symptoms may develop, resulting in systemic effects. Signs and symptoms of a hormonally active tumor include labile hypertension, increased heart rate, headache, excessive sweating, tremors, as well as facial flushing; these mandate a comprehensive evaluation.[4] A 24-hour urinary collection for catecholamines and metanephrines needs to be ordered in these cases. Plasma metanephrine testing can also be requested.

History and Physical

Patients present most commonly with hearing loss, pulsatile tinnitus, and lower cranial nerve neuropathy.[2][4][6] These symptoms can occur in up to 75% of the patients. Lower cranial nerve deficits are encountered in up to 10% of cases and can present with neurological deficits, resulting in facial palsy, dysphagia, hoarseness, shoulder weakness, and tongue deviation.[2][6][9] Other signs and symptoms include earache, ear discharge, and ear bleeding.

Evaluation

Otoscopic Examination

The most common finding on physical examination is a pulsatile red middle ear mass behind an intact tympanic membrane.[6] The tympanic membrane can show increased vascularity associated with an inferiorly based red ear mass, giving the characteristic rising sun appearance. Sometimes, the tympanic portion of the tumor may erode into the ear canal, resulting in otorrhagia.[6]

Audiologic Testing

Pure tone and speech audiometry should be performed.

Head computed tomographic scan with fine-cuts at the temporal bone demonstrate bone destruction. Bone erosion is sometimes called a moth-eaten appearance.[4]

Magnetic Resonance Imaging (MRI)

MRI with intravenous contrast-enhancement shows an enhancing lesion usually extending from the jugular bulb to the middle ear. Posterior fossa and cervical extension are common in untreated tumors. Vascular flow voids are described with the characteristic “salt-and-pepper” appearance on T1 and T2 weighted images. The MRI depicts the tumor vascularity, extension along neural foramina and multicentricity, and should be the first imaging study when evaluating a patient with a suspected glomus jugulare. On T1 weighted images without intravenous contrast, paragangliomas can appear hypointense with a speckled appearance; however, on intravenous gadolinium-enhanced contrast sequences, pronounced enhancement is seen secondary to the hypervascular nature of the glomus jugulare.[4]

Angiography

Angiography helps differentiate paragangliomas from other pathologies but also can help to demonstrate the tumor blush and the feeding vessels, which can then be embolized. The principal feeding artery is the ascending pharyngeal artery, although the occipital artery can also contribute; both branches of the external carotid artery.[4] Branches of the internal carotid artery and the vertebrobasilar system have also been reported, including the caroticotympanic artery and the posterior inferior cerebellar artery.[4] Balloon test occlusion studies can be performed to help decide whether occlusion of the petrous internal carotid artery would be tolerated.[10]

Tumor Classifications

Those described by Fisch and by Glasscock-Jackson are the most commonly used, which are based on the location and extension of the tumor.[11][12][13][12]

Treatment / Management

Observation provides an excellent treatment alternative, as 65% of the tumors remained stable and sometimes regressed in size.[14] Approximately 40% of the tumors demonstrated growth at an average of 0.9 mm per year.[15] If a patient is diagnosed with a glomus jugulare and a decision for observation is made, close follow up is necessary with serial brain MRI with and without intravenous contrast to assess the nature and behavior of the disease.(B2)

There are different therapeutic options aimed at improving local control and minimizing associated treatment morbidity; however, the management of glomus tumors continues to be a challenge.[4] There are still many controversies regarding optimal treatment. Historically, the treatment of this tumor involved surgical resection, external beam radiotherapy (EBRT), or a combination of both.[1] However, these treatment options carry a significant risk of morbidity, and as a result, stereotactic radiosurgery (SRS) has become an increasingly popular treatment.[1] A systematic review of the literature shows that EBRT and SRS are comparable to surgical intervention in patients with jugular paragangliomas.[16] The treatment decision should be individualized in each patient.(A1)

For young, healthy patients with functional cranial nerve deficits, the mainstay treatment of choice is surgical removal. Preoperative embolization is generally performed 24 to 72 hours before surgery.[10] In about 80% of patients, complete resection may be accomplished, but it may result in debilitating cranial neuropathy. New postoperative cranial nerve injuries occur in 60% of patients, involving IX X, XI, and XII. Subtotal resection has been used more frequently to minimize morbidity and improve symptoms associated with the disease.[15](B2)

Sub-total resection followed by radiosurgery for the residual tumor yields a better outcome with lower morbidity and mortality.[17] As an adjunct for surgical intervention, endoscopy has been used and is associated with smaller incisions and tailored trajectories, however, this is mostly reserved for posterior fossa extensions. Advances in technology have provided nerve monitoring techniques that are used during evaluation and to prevent lower cranial nerve damage during surgery.

Radiation can be utilized in the setting of bilateral glomus jugulare tumors and can represent an adjunct to limited surgical approaches with associated subtotal resection.[4] Modalities include standard fractionated radiotherapy and stereotactic radiosurgery. Standard fractionated radiotherapy requires multiple sessions while radiosurgery can be given in a single session providing focused radiation and, at the same time, sparring the vulnerable structures inside the tympanic bone.[4] It can be offered as an adjunctive to limited surgery or as the primary treatment modality in poor surgical candidates or patients with bilateral disease providing up to 90% control rate.[4][18] Radiosurgery alone (systematic review and meta-analysis) provides tumor control in 92% of the patients, symptom control in 93%, with 8% of complications.[19][20] For local control, ≥ 90%, a recommended median marginal dose of 15 Gy (range, 12-30 Gy) should be given.[5](A1)

Complete obliteration of glomus jugulare tumors with the use of embolization is very difficult and is prone to revascularization and is not beneficial in terms of alleviating clinical symptoms.[21] Endovascular embolization, as a single modality of treatment, is considered palliative.[4] Onyx embolization can be used for palliative management of otorrhagia in patients with unresectable tumors.[22] Preoperative embolization of the tumor can lead to a decrease in the duration of surgery, as well as a reduction of operative estimated blood loss.[4](B3)

Differential Diagnosis

• Schwannoma of lower cranial nerves
• Neuroma of lower cranial nerves
• Glomus tympanicum
• Neck and head metastasis
• Bone metastasis
• Lymph node metastasis
• Meningioma
• Cholesteatoma
• Endolymphatic sac tumors
• Chordoma
• Chondrosarcoma
• Epidermoid
• Chronic mastoiditis
• Hemangiopericytoma
• Plasmacytoma
• Dural arteriovenous fistula
• Arteriovenous malformations
• High riding jugular bulb
• Asymmetry of jugular foramen size
• Tortuous internal carotid artery
• Idiopathic intracranial hypertension[23]

Prognosis

Recent series show a stroke rate of 0% to 3.5%, a cranial nerve injury rate of 5%-39%, and overall mortality of 0%-2.7%, with 15% of the patients unable to return to their preoperative daily activities.[24]

With stereotactic radiosurgery treatment, 60% of the patients showed improvement of previous neurological deficits. Tumor control is obtained in 91% of the patients.[25] The Kaplan-Meier tumor control rate is 92.2% at five years and 86.3% at ten years.[26] Hearing tends to worsen post radiosurgery; however, balance, dizziness, and tinnitus usually improve post radiosurgery.[27]

Complications

• Sigmoid sinus thrombosis
• Cranial neuropathies
• Pulsatile tinnitus
• Deterioration of hearing
• Vocal cord paralysis
• Aspiration
• Facial paralysis
• Conductive hearing loss
• Cerebrospinal fluid leak
• Lower cranial neuropathy
• Temporal bone osteoradionecrosis
• Brain radionecrosis